Fig. 1.

Scheme of participation of MC1R in regulation of melanogenesis. ACTH or α-, β-, or γ-melanocyte-stimulating hormone binding evokes cAMP level increase due to the activation of adenylate cyclase (AC), the induction of MITF, which in turn promotes the expression of a number of proteins including tyrosinase and hence the production of melanin. This pathway is inhibited by extracellular regulators, ASIP via MC1R binding and attractin (ATTR) and β-defensin 3 (BD3), as well as by a variety of intracellular regulatory proteins (MRAP, MGRN1, GRK2). In addition, due to GRK6 phosphorylation and subsequent ARRB2 binding, activated MC1R undergoes endocytosis. In turn, the effect of GRK6 is controlled by competition with ARRB1, which also binds to MC1R but does not induce endocytosis.